High-dimensional profiling of regulatory T cells in psoriasis reveals an impaired skin-trafficking propertyResearch in context
Summary: Background: Psoriasis is a chronic inflammatory skin disease with a Th17-skewed immune phenotype. Although it has been generally accepted that regulatory T cells (Tregs) in lesional psoriatic skin have functional impairment due to the local inflammatory microenvironment, the molecular prop...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396424000203 |
| _version_ | 1797334725676761088 |
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| author | Brian Hyohyoung Lee Yoon Ji Bang Sung Ha Lim Seong-Jun Kang Sung Hee Kim Seunghee Kim-Schulze Chung-Gyu Park Hyun Je Kim Tae-Gyun Kim |
| author_facet | Brian Hyohyoung Lee Yoon Ji Bang Sung Ha Lim Seong-Jun Kang Sung Hee Kim Seunghee Kim-Schulze Chung-Gyu Park Hyun Je Kim Tae-Gyun Kim |
| author_sort | Brian Hyohyoung Lee |
| collection | DOAJ |
| description | Summary: Background: Psoriasis is a chronic inflammatory skin disease with a Th17-skewed immune phenotype. Although it has been generally accepted that regulatory T cells (Tregs) in lesional psoriatic skin have functional impairment due to the local inflammatory microenvironment, the molecular properties of skin-homing psoriatic Tregs have not been well explored. Methods: We designed an extensive 39 marker mass cytometry (CyTOF) panel to deeply profile the immune landscape of skin-homing Tregs from 31 people with psoriasis stratified by psoriasis area severity index score as mild (n = 15) to moderate-severe (n = 16) and 32 healthy controls. We further validated the findings with an in-vitro chemokine-mediated Treg migration assay, immunofluorescent imaging of normal and psoriatic lesional skin and analysed public single-cell RNA-sequencing datasets to expand upon our findings into the local tissue microenvironments. Findings: We discovered an overall decrease in CLAhi Tregs and specifically, CLAhiCCR5+ Tregs in psoriasis. Functional markers CD39 and FoxP3 were elevated in psoriatic Tregs. However, CCR7 expression was significantly increased while CCR4 and CLA expression was reduced in psoriatic Tregs and CLAhi Tregs, which was associated with disease severity. Moreover, psoriatic Tregs revealed increased migratory capacity towards CCR7’s ligands, CCL19/CCL21. Interrogation of public single-cell RNA sequencing data confirmed reduced expression of skin-trafficking markers in lesional-skin Tregs compared to non-lesioned skin, further substantiated by immunofluorescent staining. Interpretation: Psoriatic circulating Tregs showed an impaired skin-trafficking phenotype thus leading to insufficient suppression of ongoing inflammation in the lesional skin, expanding upon our current understanding of the impairment of Treg-mediated immunosuppression in psoriasis. Funding: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science and Information and Communications Technology (2020R1C1C1014513, 2021R1A4A5032185, 2020R1F1A1073692); and the new faculty research seed money grant of Yonsei University College of Medicine for 2021 (2021-32-0033). |
| first_indexed | 2024-03-08T08:26:19Z |
| format | Article |
| id | doaj.art-40a784037ed5475d80b773ce5c94340c |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-03-08T08:26:19Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-40a784037ed5475d80b773ce5c94340c2024-02-02T04:39:40ZengElsevierEBioMedicine2352-39642024-02-01100104985High-dimensional profiling of regulatory T cells in psoriasis reveals an impaired skin-trafficking propertyResearch in contextBrian Hyohyoung Lee0Yoon Ji Bang1Sung Ha Lim2Seong-Jun Kang3Sung Hee Kim4Seunghee Kim-Schulze5Chung-Gyu Park6Hyun Je Kim7Tae-Gyun Kim8Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, South Korea; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USADepartment of Biomedical Sciences, Seoul National University Graduate School, Seoul, South KoreaDepartment of Dermatology, Yonsei University Wonju College of Medicine, Wonju, South KoreaDepartment of Biomedical Sciences, Seoul National University Graduate School, Seoul, South Korea; Cancer Research Institute, Seoul National University, Seoul, South KoreaDepartment of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, South KoreaHuman Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USADepartment of Biomedical Sciences, Seoul National University Graduate School, Seoul, South Korea; Cancer Research Institute, Seoul National University, Seoul, South Korea; Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, South Korea; Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul, South Korea; Transplantation Research Institute, Seoul National University Medical Research Center, Seoul, South Korea; Seoul National University Hospital, Seoul, South Korea; Corresponding author. Department of Biomedical Science, Seoul National University Graduate School, Seoul, South Korea.Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, South Korea; Cancer Research Institute, Seoul National University, Seoul, South Korea; Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, South Korea; Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul, South Korea; Seoul National University Hospital, Seoul, South Korea; Genome Medicine Institute, Seoul National University Medical Research Center, Seoul, South Korea; Corresponding author. Department of Biomedical Science, Seoul National University Graduate School, Seoul, South Korea.Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, South Korea; Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea; Corresponding author. Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea.Summary: Background: Psoriasis is a chronic inflammatory skin disease with a Th17-skewed immune phenotype. Although it has been generally accepted that regulatory T cells (Tregs) in lesional psoriatic skin have functional impairment due to the local inflammatory microenvironment, the molecular properties of skin-homing psoriatic Tregs have not been well explored. Methods: We designed an extensive 39 marker mass cytometry (CyTOF) panel to deeply profile the immune landscape of skin-homing Tregs from 31 people with psoriasis stratified by psoriasis area severity index score as mild (n = 15) to moderate-severe (n = 16) and 32 healthy controls. We further validated the findings with an in-vitro chemokine-mediated Treg migration assay, immunofluorescent imaging of normal and psoriatic lesional skin and analysed public single-cell RNA-sequencing datasets to expand upon our findings into the local tissue microenvironments. Findings: We discovered an overall decrease in CLAhi Tregs and specifically, CLAhiCCR5+ Tregs in psoriasis. Functional markers CD39 and FoxP3 were elevated in psoriatic Tregs. However, CCR7 expression was significantly increased while CCR4 and CLA expression was reduced in psoriatic Tregs and CLAhi Tregs, which was associated with disease severity. Moreover, psoriatic Tregs revealed increased migratory capacity towards CCR7’s ligands, CCL19/CCL21. Interrogation of public single-cell RNA sequencing data confirmed reduced expression of skin-trafficking markers in lesional-skin Tregs compared to non-lesioned skin, further substantiated by immunofluorescent staining. Interpretation: Psoriatic circulating Tregs showed an impaired skin-trafficking phenotype thus leading to insufficient suppression of ongoing inflammation in the lesional skin, expanding upon our current understanding of the impairment of Treg-mediated immunosuppression in psoriasis. Funding: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science and Information and Communications Technology (2020R1C1C1014513, 2021R1A4A5032185, 2020R1F1A1073692); and the new faculty research seed money grant of Yonsei University College of Medicine for 2021 (2021-32-0033).http://www.sciencedirect.com/science/article/pii/S2352396424000203Chemokine receptorsMass cytometryPsoriasisRegulatory T cellsSkin-trafficking |
| spellingShingle | Brian Hyohyoung Lee Yoon Ji Bang Sung Ha Lim Seong-Jun Kang Sung Hee Kim Seunghee Kim-Schulze Chung-Gyu Park Hyun Je Kim Tae-Gyun Kim High-dimensional profiling of regulatory T cells in psoriasis reveals an impaired skin-trafficking propertyResearch in context EBioMedicine Chemokine receptors Mass cytometry Psoriasis Regulatory T cells Skin-trafficking |
| title | High-dimensional profiling of regulatory T cells in psoriasis reveals an impaired skin-trafficking propertyResearch in context |
| title_full | High-dimensional profiling of regulatory T cells in psoriasis reveals an impaired skin-trafficking propertyResearch in context |
| title_fullStr | High-dimensional profiling of regulatory T cells in psoriasis reveals an impaired skin-trafficking propertyResearch in context |
| title_full_unstemmed | High-dimensional profiling of regulatory T cells in psoriasis reveals an impaired skin-trafficking propertyResearch in context |
| title_short | High-dimensional profiling of regulatory T cells in psoriasis reveals an impaired skin-trafficking propertyResearch in context |
| title_sort | high dimensional profiling of regulatory t cells in psoriasis reveals an impaired skin trafficking propertyresearch in context |
| topic | Chemokine receptors Mass cytometry Psoriasis Regulatory T cells Skin-trafficking |
| url | http://www.sciencedirect.com/science/article/pii/S2352396424000203 |
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